Back to resultsTreatment of Malignant Melanoma With GPA-TriMAR-T Cell Therapy
Primary Purpose
Malignant Melanoma
Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
GPA-TriMAR-T
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Melanoma focused on measuring HLA-A2, gp100
Eligibility Criteria
Inclusion Criteria:
- All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
- All subjects must be able to comply with all the scheduled procedures in the study;
- HLA_A2 genotype and gp100 positive malignant melanoma： Ⅳ stage or relapsed after surgery or chemotherapy or no available standard therapy;
- At least one measurable lesion per RECIST V1.1;
- Aged 18 to 69 years;
- Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤2;
- Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
- All other treatment induced adverse events must have been resolved to ≤grade 1;
- Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB>70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);
Exclusion Criteria:
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment);
- Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator;
- Lactating women or women of childbearing age who plan to conceive during the time period;
- Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
- Known history of infection with HIV;
- Subjects need systematic usage of corticosteroid;
- Subjects need systematic usage of immunosuppressive drug;
- Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
- Other reasons the investigator consider the patient may not be suitable for the study.
Sites / Locations
- Hainan Cancer HospitalRecruiting
- The Second Affiliated Hospital of Hainan Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GPA-TriMAR-T
Arm Description
Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells, and these cells will then be infused back into the patient for intervention.
Outcomes
Primary Outcome Measures
safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
Secondary Outcome Measures
Complete response rate[CR] （Complete response rate per the revised International Working Group (IWG) Response Criteria）
Complete response rate per the revised International Working Group (IWG) Response Criteria
Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
Partial response rate per the revised International Working Group (IWG) Response Criteria
Duration of Response （The time from response to relapse or progression）
The time from response to relapse or progression
Progression Free Survival （The time from the first day of treatment to the date on which disease progresses.）
The time from the first day of treatment to the date on which disease progresses.
Overall Survival （The number of patient alive, with or without signs of cancer）
The number of patient alive, with or without signs of cancer
Full Information
NCT ID
NCT03649529
First Posted
August 23, 2018
Last Updated
December 5, 2019
Sponsor
Timmune Biotech Inc.
Collaborators
The Second Affiliated Hospital of Hainan Medical University, Hainan Cancer Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03649529
Brief Title
Treatment of Malignant Melanoma With GPA-TriMAR-T Cell Therapy
Official Title
Adoptive Immunotherapy for HLA_A2 Genotype gp100 Positive Malignant Melanoma With GPA-TriMAR-T Cell
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 27, 2018 (Actual)
Primary Completion Date
September 15, 2021 (Anticipated)
Study Completion Date
January 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Timmune Biotech Inc.
Collaborators
The Second Affiliated Hospital of Hainan Medical University, Hainan Cancer Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Malignant melanoma have been reported to be characterized with high gp100 expression. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the GPA-TriMAR-T cells will recognize and kill target cells that express gp100(209-217) peptides in the form MHC-I complex, thus eliminating malignant melanoma from the body.
Detailed Description
GPA-TriMAR is a modified chimeric antigen receptor (CAR) that consist of three subunit in it's outer membrane domain. The outer membrane domain linked to the inner membrane 4-1BB/CD3ζ domain through the transmembrane domain, thus compose the complete chimeric antigen receptor. Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells. When infused back to the patient, the modified GPA-TriMAR-T cells will recognize and kill malignant melanoma cells in the body, and in the meanwhile the other two subunits function to stimulate the innate immune system and enhance GPA-TriMAR-T cells tumor Infiltration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
Keywords
HLA-A2, gp100
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells,and then infused back into the patient.
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
GPA-TriMAR-T
Arm Type
Experimental
Arm Description
Patients' autologous T cells will be isolated and transduced by GPA-TriMAR lentivirus to generate the GPA-TriMAR-T cells, and these cells will then be infused back into the patient for intervention.
Intervention Type
Biological
Intervention Name(s)
GPA-TriMAR-T
Other Intervention Name(s)
TCR-mimic-CAR-T
Intervention Description
Patients will undergo leukapheresis to isolate autologous T cells, these T cells will be activated and modified to express GPA-TriMAR in the manufacture facility, and eventually infused back into the body for treatment.
Primary Outcome Measure Information:
Title
safety （Incidence of treatment-related adverse events as assessed by CTCAE v4.03）
Description
Incidence of treatment-related adverse events as assessed by CTCAE v4.03
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Complete response rate[CR] （Complete response rate per the revised International Working Group (IWG) Response Criteria）
Description
Complete response rate per the revised International Working Group (IWG) Response Criteria
Time Frame
24 months
Title
Partial response rate [PR] （Partial response rate per the revised International Working Group (IWG) Response Criteria）
Description
Partial response rate per the revised International Working Group (IWG) Response Criteria
Time Frame
24 months
Title
Duration of Response （The time from response to relapse or progression）
Description
The time from response to relapse or progression
Time Frame
24 months
Title
Progression Free Survival （The time from the first day of treatment to the date on which disease progresses.）
Description
The time from the first day of treatment to the date on which disease progresses.
Time Frame
24 months
Title
Overall Survival （The number of patient alive, with or without signs of cancer）
Description
The number of patient alive, with or without signs of cancer
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
All subjects must be able to comply with all the scheduled procedures in the study;
HLA_A2 genotype and gp100 positive malignant melanoma： Ⅳ stage or relapsed after surgery or chemotherapy or no available standard therapy;
At least one measurable lesion per RECIST V1.1;
Aged 18 to 69 years;
Expected survival ≥12 weeks; Eastern cooperative oncology group (ECOG) performance status of≤2;
Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
All other treatment induced adverse events must have been resolved to ≤grade 1;
Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB>70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);
Exclusion Criteria:
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment);
Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator;
Lactating women or women of childbearing age who plan to conceive during the time period;
Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
Known history of infection with HIV;
Subjects need systematic usage of corticosteroid;
Subjects need systematic usage of immunosuppressive drug;
Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
Other reasons the investigator consider the patient may not be suitable for the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haifeng Lin
Phone
+86 13322060949
Email
13322060949@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Bin Gao
Phone
+86 13910899150
Email
bin.gaoa@timmune.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Haifeng Lin
Organizational Affiliation
The Second Affiliated Hospital of Hainan Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hainan Cancer Hospital
City
Haikou
State/Province
Hainan
ZIP/Postal Code
570100
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuyang Tian
Phone
+86 18686853849
Email
tianyuyang@163.com
Facility Name
The Second Affiliated Hospital of Hainan Medical University
City
Haikou
State/Province
Hainan
ZIP/Postal Code
570100
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haifeng Lin
Phone
+86 13322060949
Email
13322060949@163.com
First Name & Middle Initial & Last Name & Degree
Yasong Wu
Phone
+86 18020091931
Email
yasong.wu@timmune.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24389689
Citation
Zhang G, Wang L, Cui H, Wang X, Zhang G, Ma J, Han H, He W, Wang W, Zhao Y, Liu C, Sun M, Gao B. Anti-melanoma activity of T cells redirected with a TCR-like chimeric antigen receptor. Sci Rep. 2014 Jan 6;4:3571. doi: 10.1038/srep03571.
Results Reference
background
PubMed Identifier
24100387
Citation
Zhang G, Liu R, Zhu X, Wang L, Ma J, Han H, Wang X, Zhang G, He W, Wang W, Liu C, Li S, Sun M, Gao B. Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody. Immunol Cell Biol. 2013 Nov-Dec;91(10):615-24. doi: 10.1038/icb.2013.45. Epub 2013 Oct 8.
Results Reference
background
PubMed Identifier
28925994
Citation
Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.
Results Reference
background
Learn more about this trial
Treatment of Malignant Melanoma With GPA-TriMAR-T Cell Therapy
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